In a phase III trial reported in the Journal of Clinical Oncology, Suresh S. Ramalingam, MD, and colleagues found that the addition of the poly (ADP-ribose) polymerase inhibitor veliparib to platinum-based chemotherapy did not improve overall survival in current smokers with previously untreated advanced squamous cell non–small cell lung cancer (NSCLC), the primary endpoint of the trial. A trend toward improvement was observed among all patients and in a subgroup with tumors with more nonadenocarcinoma molecular characteristics.

Suresh S. Ramalingam, MD

Study Details

In the double-blind trial, 970 patients from sites in 37 countries were randomly assigned between April 2014 and November 2019 to receive veliparib at 120 mg twice daily (n = 486) or placebo (n = 484) together with carboplatin at area under the curve = 6 and paclitaxel at 200 mg/m² on day 1 of 21-day cycles for up to six cycles. A total of 276 patients (57%) in each group were current smokers. The primary endpoint of the study was overall survival among current smokers.

Biomarker analysis of tumor samples was performed using a 52-gene expression histology classifier (LP52) to identify tumors with greater nonadenocarcinoma vs adenocarcinoma molecular characteristics (LP52-positive tumors).

Overall Survival

At time of primary data cut-off, median follow-up for overall survival was 19.3 months and 20.6 months for current smokers in the veliparib and placebo groups, respectively. Median overall survival among current smokers was 11.9 months (95% confidence interval [CI] = 10.5–13.5 months) in the veliparib group vs 11.1 months (95% CI = 9.6–2.6 months) in the placebo group (hazard ratio [HR] = 0.905, 95% CI = 0.744–1.101, P = .266).

In the overall population, median overall survival was 12.2 months (95% CI = 10.9–13.5 months) in the veliparib group vs 11.2 months (95% CI = 10.1–12.6 months) in the placebo group (HR = 0.853, 95% CI = 0.747–0.974, nominal P = .032). Median progression-free survival was 5.6 months (95% CI = 5.6–5.8) with veliparib vs 5.6 months (95% CI = 5.5–5.7 months) with placebo (HR = 0.897, 95% CI = 0.779–1.032, P = .107). Approximately half of all patients received posttreatment anticancer therapy, which was comparable between groups.

Among a total of 360 patients in whom LP52 status could be determined, 202 (56%) were LP52-positive, including 94 in the veliparib group and 108 in the placebo group; the 158 LP52-negative patients included 85 in the veliparib group and 73 in the placebo group. Among LP52-positive patients, median overall survival was 14.0 months (95% CI = 11.9–19.2 months) in the veliparib group vs 9.6 months (95% CI = 8.8–12.8 months) in the placebo group (HR = 0.66, 95% CI = 0.49–0.89). Among LP52-negative patients, median overall survival was 11.0 months (95% CI = 8.2–14.7) with veliparib vs 14.4 months (95% CI = 10.6–17.5 months) with placebo (HR = 1.33, 95% CI = 0.95–1.86). In the placebo group, LP52-negative status was associated with better survival (HR = 1.6, 95% CI = 1.15–2.22). Median progression-free survival was 5.78 vs 5.62 months (HR = 0.79, 95% CI = 0.57–1.08) among LP52-positive patients and 5.59 vs 5.88 months (HR = 1.38, 95% CI = 0.97–1.98) among LP52-negative patients.

Adverse Events

Among all patients, grade ≥ 3 adverse events occurred in 60% of those in the veliparib group and 58% of the placebo group, consisting of primarily hematologic events (neutropenia in 24% vs 20% and anemia in 10% vs 11%). Serious adverse events occurred in 32% vs 34% of patients, with pneumonia, febrile neutropenia, and anemia being the most common in both groups (each in ≤ 5% of patients). Adverse events led to discontinuation of veliparib and placebo in 21% and 23% of patients, respectively.

The investigators concluded, “In current smokers with advanced squamous cell NSCLC, there was no therapeutic benefit of adding veliparib to first-line chemotherapy. The LP52 signature may identify a subgroup of patients likely to derive benefit from veliparib with chemotherapy.”

Dr. Ramalingam, of Winship Cancer Institute, Emory University School of Medicine, is the corresponding author for the Journal of Clinical Oncology article.

Disclosure: The study was funded by AbbVie. For full disclosures of the study authors, visit ascopubs.org.